Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The field of acid suppression has been advanced by therapeutics of increasing specificity for inhibiting gastric acid secretion. Particularly important are proton pump inhibitors (PPIs), which inhibit the activity of the gastric acid pump (H+,K(+)-adenosine triphosphatase), the final common step in gastric acid production. Histamine2-receptor antagonists, which act at an early stage of the acid secretion pathway, are less effective and are subject to intolerance. The PPIs are weak bases that undergo accumulation in the acidic space of the secreting parietal cell and are converted in acid to the active thiophilic form, which then forms disulfide bonds with key cysteines of the gastric acid pump. Pantoprazole differs from other PPIs in terms of its reaction with cysteine 822 in the pump and with cysteine 813, a common binding site for all PPIs. Both cysteines are in the sixth transmembrane segment, which is part of the ion transport pathway. This selective binding may have an impact on the dwell time of pantoprazole versus other PPIs because it is inaccessible to reducing agents, in contrast to cysteine 813. Pantoprazole is also very stable (has a slow rate of activation) at neutral pH values compared with other PPIs and has a relatively robust plasma concentration-time curve. These agents are important in the management of duodenal ulcers, nonsteroidal antiinflammatory drug-induced ulcers, gastroesophageal reflux disease, and dyspepsia, but basic pharmacokinetic and pharmacodynamic differences among them may affect clinical utility.
 ...
PMID:Physiology of the parietal cell and therapeutic implications. 1458 60

A multitarget herbal preparation, STW 5, has been used clinically in different gastro-intestinal disorders including functional dyspepsia and irritable bowel syndrome. Previous studies have shown that it possesses properties that may render it useful in gastro-oesophageal reflux disease (GERD). We performed this study to test this compound in an acute model of reflux oesophagitis in rats. Oesophagitis was induced surgically by ligating the pyloric end and fore-stomach. Lower oesophageal pH was measured 3 h later in conscious animals. Five hours after surgery, animals were sacrificed and the oesophagi were examined macroscopically and histologically. Selected markers of inflammation were measured in oesophageal homogenates. STW 5 was given orally for 5 days before induction of oesophagitis. Pantoprazole was used as a reference standard. Ligated animals showed a high incidence of ulcerative lesions associated with a marked increase in myeloperoxidase, thiobarbituric acid-reactive substances, tumor necrosis factor-alpha, and interleukin-1beta. STW 5 did not affect oesophageal pH, but dose-dependently reduced the severity of the oesophageal lesions and normalized the deranged level of the inflammation markers. The beneficial effects were confirmed histopathologically. STW 5 proved to be effective in protecting against inflammatory lesions in this model of oesophagitis, thus warranting further investigation of its potential therapeutic usefulness in GERD.
 ...
PMID:Effect of an herbal preparation, STW 5, in an acute model of reflux oesophagitis in rats. 2048 68